根據2022 年美國糖尿病學會臨床照護指引， 類升糖素胜肽-1 受體促進劑(glucagon-like peptide-1 receptor agonists, GLP-1 RA) 可以有效控制血糖，對於動脈硬化心血管疾病及慢性腎臟病也有保護效果。過去的GLP-1 RA 皆為皮下注射劑型，使用起來不如口服劑型方便，也可能導致服藥順從性較低。2021 年8 月於臺灣核准上市使用的semaglutide (Rybelsus®)，係透過氨基酸結構修飾替換與複合吸收促進劑，克服藥物易被胃酸分解問題，成為第一個GLP-1 RA 口服劑型藥物。本文主要介紹GLP-1 RA 口服劑型藥物之技術，並整理口服semaglutide 效果和安全性的相關臨床證據。相較於安慰劑，口服劑型的semaglutide 可顯著降低約1.0% glycated hemoglobin (HbA1c)（95% 信賴區間：−0.8 ~ −1.3%） 以及減少體重2.5 kg（95% 信賴區間：−1.7 ~ −3.4 kg）；相較於其他降血糖藥物，可顯著降低約0.3% HbA1c（95% 信賴區間：−0.2 ~ −0.5%）以及減少體重1.5 kg（95% 信賴區間：−0.9 ~ −2.2 kg）。另外，相較於安慰劑，口服劑型的semaglutide 能降低43% 的總死亡率風險，但是在整體不良事件發生率與安慰劑或其他降血糖藥物相比並無明顯差異，惟有較高比例腸胃道不良事件（包含噁心、嘔吐、腹瀉）。目前現有實證數據多來自於臨床試驗，期望未來更多大型真實世界與長期追蹤的研究，以確立口服劑型semaglutide 在臨床實務上的效益。
The 2022 American Diabetes Association guidelines suggest the use of glucagonlike peptide-1 receptor agonists (GLP-1 RAs) to control blood glucose levels and provide additional protective effects in regard to atherosclerotic cardiovascular diseases and chronic kidney diseases. However, all available GLP-1 RA’s in the past have required subcutaneous injection, raising lingering issues of inconvenience and poor drug adherence. Through an amino acid substitution and conformation with an absorption enhancer, the new oral form GLP-1 RA has overcome the issue of drug degradation by gastric acid. Semaglutide (Rybelsus®), approved by the Taiwan Food and Drug Administration in August 2021, has become the first GLP-1 RA for oral administration. This article provides an overview of techniques for oral semaglutide use and a review of the evidence on efficacy and safety of the drug. In summary, compared to the placebo group, patients receiving oral semaglutide showed a 1.0% glycated hemoglobin (HbA1c) reduction (95% confidence intervals [CIs], −0.8 to −1.3%) and a 2.5 kg body weight reduction (95% CIs, −1.7 to −3.4). Compared to other diabetes medications, patients receiving oral semaglutide showed a 0.3% HbA1c reduction (95% CIs, −0.2 to −0.5%) and a 1.5 kg body weight reduction (95% CIs, −0.9 to −2.2). Compared to placebo, oral semaglutide could lower 43% of all-cause death risk, but there was no difference in the risk of adverse events compared to placebo or other diabetes medication groups, except that the incidence of gastrointestinal events was higher. Because current evidence is predominantly based on randomized controlled trials, further large-scale studies with longer observational periods are required to ensure the effectiveness of oral semaglutide in real-world practice.
Submitted for publication: 2022.2.12; Accepted for publication: 2022.10.18
